A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients
A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients
复制标题
DOI：
10.1097/ftd.0000000000000580
复制
发表时间：
2019-02-01
影响因子：
2.5
通讯作者：
Warren, David John
中科院分区：
文献类型：
--
作者：
Klaasen, Rolf Anton;Egeland, Erlend Johannessen;Warren, David John
背景资料：贝拉西普（Nulojix; Bristol-Myers Squibb，纽约，NY）是一种用于预防肾移植后急性排斥反应的生物免疫抑制药物。很少有研究描述了贝拉西普的药代动力学，治疗药物监测的效果尚未调查。我们已经开发了一种药物捕获法（使用药物靶点）来测量血清中的贝拉西普，并应用此方法在肾移植recipients.Methods的药代动力学研究：CD 80被用来捕获贝拉西普到链霉亲和素包被的威尔斯孔。使用Eu 3+标记的蛋白A和时间分辨荧光定量捕获的药物。该试验应用于接受贝拉西普输注的肾移植患者的初步药代动力学研究。在贝拉西普输注之间的几个时间点测定贝拉西普血清浓度。结果：测定范围为0.9 ~ 30 mg/L，准确度为91%~ 99%，变异系数为1.2%~ 3.6%。前稀释法的测量范围为130 mg/L，准确度为90%，变异系数为3.8%。样品在48 ℃下储存15天和2次冻融循环期间稳定。在26个输注间隔期间从5名肾移植受者收集的总共203份血清样品中测定贝拉西普浓度。人口药代动力学模型可视化测量和预测concentration.Conclusions：我们已经开发出一种自动化的，准确的，精确的测定贝拉西普血清浓度。该检测方法已成功应用于接受贝拉西普输注的肾移植受者的药代动力学研究。
Background: Belatacept (Nulojix; Bristol-Myers Squibb, New York, NY) is a biological immunosuppressive drug used for the prophylaxis of acute rejection after renal transplantation. Few studies have described belatacept pharmacokinetics, and the effect of therapeutic drug monitoring has not been investigated. We have developed a drug-capture assay (using drug target) to measure belatacept in serum and applied this assay in a pharmacokinetic study in renal transplant recipients.Methods: CD80 was used to trap belatacept onto streptavidin-coated wells. Captured drug was quantified using Eu3+-labeled protein A and time-resolved fluorescence. The assay was applied in a pilot pharmacokinetic study in renal transplanted patients receiving belatacept infusions. Belatacept serum concentrations were determined at several time points between belatacept infusions. A simple population pharmacokinetic model was developed to visualize measured and predicted belatacept serum concentrations.Results: The assay range was 0.9-30 mg/L with accuracy within 91%-99% and coefficients of variation ranging from 1.2% to 3.6%. Predilution extended the measurement range to 130 mg/L with an accuracy of 90% and coefficients of variation of 3.8%. Samples were stable during storage at 48 degrees C for 15 days and during 2 freeze-thaw cycles. Belatacept concentrations were determined in a total of 203 serum samples collected during 26 infusion intervals from 5 renal transplant recipients. The population pharmacokinetic model visualized both measured and predicted concentrations.Conclusions: We have developed an automated, accurate, and precise assay for the determination of belatacept serum concentrations. The assay was successfully applied in a pharmacokinetic study in renal transplant recipients receiving belatacept infusions.